Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance

Abstract

Background: The UK Thalassaemia Register records births, deaths and selected clinical data of patients with thalassaemia who are resident in the UK. A study of survival and causes of death was undertaken which aimed to include the possible impact of T2* cardiovascular magnetic resonance (CMR).

Methods: The Register was updated to the end of 2003, copies of death certificates were obtained, and causes of death in beta thalassaemia major were extracted. In addition, patients who had T2* CMR assessment of cardiac iron load and/or received the oral iron chelator deferiprone were identified from clinical records.

Results: The main causes of death were anaemia (before 1980), infections, complications of bone marrow transplantation and cardiac disease due to iron overload. From 1980 to 1999 there were 12.7 deaths from all causes per 1,000 patient years. Forty per cent of patients born before 1980 had T2* cardiovascular magnetic resonance between 2000 and 2003, and 36% of these patients were prescribed deferiprone before end of 2003. In 2000-2003, the death rate from all causes fell significantly to 4.3 per 1,000 patient years (-62%, p < 0.05). This was mainly driven by the reduction in the rate of deaths from iron overload which fell from 7.9 to 2.3 deaths per 1,000 patient years (-71%, p < 0.05).

Conclusion: Since 1999, there has been a marked improvement in survival in thalassaemia major in the UK, which has been mainly driven by a reduction in deaths due to cardiac iron overload. The most likely causes for this include the introduction of T2* CMR to identify myocardial siderosis and appropriate intensification of iron chelation treatment, alongside other improvements in clinical care.

Figure 1

Number of deaths of patients with thalassaemia major in the UK by intervals. The number of deaths in the 2000–2003 interval represents deaths during 4 years, and in all the other groups the number of deaths is over 5 years. Iron overload replaced anaemia as the commonest cause of death after 1970, when adequate transfusion schemes became the norm. Iron chelation therapy by subcutaneous infusion of deferoxamine was standard practice after 1980. In 1999, T2* CMR was introduced in the UK, and doctors caring for thalassemia patients were informed of the high cardiac death rate and new options for iron chelation therapy. There has been a 71% reduction in the annualized death-rate from iron overload since 2000.

Figure 2

Comparison of life expectancy for patients who were alive at the beginning of 1970, 1980, 1990 and 2000, based on mortality in the subsequent five years (four years for the period 2000–2003). Curves are constructed by calculating the proportion of patients in each group who were alive at the time indicated and were still alive at the end of the next 5 years. For the four year interval 2000–2003, mortality was multiplied by 1.25 to adjust to 5 years. The calculation shows an average life-expectancy of 17 years in 1970, 27 years in 1980 and 37 years in 1990. Since 2000 over 80% of patients have a life expectancy of more than 40 years. It is still not possible to estimate ultimate life-expectancy, and the prognosis for older patients remains "open-ended".